We are continuing our studies on human melanoma, using the monoclonal antibody technique. So far, we have made monoclonal antibodies to two different glycolipid antigens, 3.1 and 4.2, and to four different protein antigens, p97, p155, p210 and 48.2, all of which are expressed on the surface of melanomas. We use quantitative assays to define antigen expression as the number of molecules of antigen per cell (whenever feasible). More antibodies are being made; in particular, we attempt to raise antibodies against primary melanomas of different histological types and compare antigen expression there with that in metastases. The degree of antigenic variation within tumors is being studied, and we also investigate the various antibodies for biological functions (complement dependent, cytotoxicity, antibody-dependent cellular cytotoxicity). We are following up on recent findings, according to which antibodies to two different epitopes of the same antigen, p97, act synergistically in complement-dependent cytotoxicity. The molecular nature of a highly melanoma associated antigen, 4.2, is being studied in collaboration with S.\I. Hakomori's group. This antigen, which is expressed in approximately 90% of human melanomas, is of potential interest as a diagnostic marker and therapeutic target. A modification of the Sternberger peroxidase-antiperoxidase technique is being extensively used to study antigen expression in histological sections of melanoma and control tissues.